Abstract
H19 is an imprinted oncofetal gene, and loss of imprinting at the H19 locus results in over-expression of H19 in cancers. Aflatoxin B1(AFB1) is regarded as one of the most dangerous carcinogens. Exposure to AFB1 would most easily increase susceptibility to diseases such as hepatocellular carcinoma(HCC) but any possible relationship between AFB1 and H19 is not clear. In present study, we found that AFB1 could up-regulate the expression of H19 and promote cell growth and invasion by hepatocellular carcinoma HepG2 cells. Knocking down H19 RNA co ld reverse the effects of AFB1 on cell growth and invasion. In addition, AFB1 induced the expression of E2F1 and its knock-down could down-regulate H19 expression and suppress cell growth and invasion in hepatocellular carcinoma HepG2 cells. Furthermore, E2F1 over-expression could up-regulate H19 expression and promote cell growth and invasion, with binding to the H19 promoter being demonstrated by chromatin immunoprecipitation assays (ChIP). In summary, our results suggested that aflatoxin B1 could promote cell growth and invasion in hepatocellular carcinoma HepG2 cells through actions on H19 and E2F1.
Highlights
Aflatoxins are secondary metabolites produced by the fungi, Aspergillus avus and Aspergillus parasiticus and usually divided four major types, aflatoxin B1, B2, G1 and G2
Our results suggested that aflatoxin B1could promote cell growth and invasion in hepatocellular carcinoma HepG2 cells through actions on H19 and E2F1
We focused our attention to investigate whether AFB1 could affect cell growth and invasion in hepatocellular carcinoma HepG2 cells through regulating H19 expression
Summary
Aflatoxins are secondary metabolites produced by the fungi, Aspergillus avus and Aspergillus parasiticus and usually divided four major types, aflatoxin B1, B2, G1 and G2. AFB1 produced by Aspergillus avus is the most potent of these toxins, and has the highest hepatocarcinogenic potential (McLean et al, 1995; IARC, 2002). The binding of AFB1 to DNA is responsible for the inhibition of RNA synthesis, which is involved in gene expression (Oyagbemi et al, 2010). It has been demonstrated that AFB1 can affect the expression of a kind of genes on mRNA level, including UDP-glucuronosyltransferase (UGT) (Hanioka et al, 2012), nuclear receptors PXR, CAR, AhR and cytochromes P450 (Ayed-Boussema et al, 2012). Yang C et al found that AFB1 treatment could increase the expression of IDH3α, and the activated PI3K/Akt pathway by IDH3α eventually neutralized the apoptosis induced by AFB1 (Yang et al, 2013). AFB1could negatively regulate Wnt/β-catenin signaling pathway through activating miR-33a (Fang et al, 2013)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
